1. Field of the Invention
This invention relates to 5-(3-substituted prop-cis-1-enyl)- and 5-(3-substituted prop-trans-1-enyl)- derivatives of 5H-dibenzo[a,d]cycloheptenes and 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes and to methods of preparing such derivatives. In a further aspect, this invention relates to 5-(3-substituted aminoprop-cis-1-enyl)- derivatives of 5H-dibenzo[a,d]cycloheptenes and 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes, and to methods of preparing such derivatives. In a still further aspect this invention relates to 5-(3-substituted aminoprop-trans-1-enyl)- derivatives of 5H-dibenzo [a,d]cycloheptenes and 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes and to methods of preparing such compounds. In another aspect, this invention relates to 5-(3-hydroxypropcis-1-enyl)- derivatives of 5H-dibenzo[a,d]cycloheptenes and 10,11-dihydro-5H-dibenzo[a,d]cycloheptenes and ethers and alkylsulfonyl esters thereof and 5-(3-hydroxyprop-trans-1-enyl)- derivatives of 5H-dibenzo[a,d]cycloheptene and 10,11-dihydro-5H-dibenzo[a,d]cycloheptene and ethers and alkylsulfonyl esters thereof and to methods of preparing such derivatives, ethers and alkylsulfonyl esters.
2. The Prior Art
Within the past 15 years, significant advances have occurred within the field of chemotherapy, especially with respect to the treatment of mental depression. One family of compounds, which have been found to be particularly useful in the treatment of endogenous depression (also referred to as melancholic or involution depression) is the family comprising dibenzazepine and dibenzocycloheptene compounds. These compounds are characterized by two benzene rings joined together by a fused cycloheptane ring. The cycloheptane ring frequently contains at least one hetero constituent such as, for example, nitrogen in the dibenzazepines, and can optionally contain a double bond in the 2-carbon atom bridge linking the two benzene rings. A further discussion of this family of compounds, including their chemotherapeutic usefulness in the treatment of mental depression can be had by reference to the literature of the prior art such as, for example, Biel, J., "Chemopharmacologic Approaches to Mental Depression", Drugs Affecting the Nervous System, Edit., Burger; Vol. 2, pages 85-125, Marcel Dekker Corp., New York (1968); and Dale, J., "Some Rationales for the Development of Anti-Depressant Drugs", Molecular Modification on Drug Design, Advances in Chemistry Series, 45, pages 114-139, 129-136, American Chemical Society, Washington, D.C. (1964); and Klerman and Cole, "Clinical Pharmacology of Imipramine and Related Anti-Depressant Compounds", Pharmacological Reviews, Vol. 17, No. 2, pages 101-141 (1965).
The tricyclic anti-depressants, e.g. imipramine, amitriptyline, etc., have been found to possess the advantage that they exhibit strong anti-depressant activity in subjects suffering from endogenous depression, yet exhibit either no activity or only very mild sedative activity in normal subjects. This is particularly important because of the difficulty of clinically distinguishing true endogenous depressive patients from patients who are merely suffering a momentary period of depression. A further and major problem compounding the difficulty of treating endogenous depression is that endogenous depression is seldom a pure depression phenomenon. Typically, there is a dominated anxiety syndrome which can be released by palliation of the depression component. Thus, pure treatment of the depression component frequently results in replacement of the dominant depression manifestation with manifestation of agitation, hostility, belligerency or other undesirable anxieties. This problem is so typically encountered that anti-depressants such as imipramine are now frequently prescribed in combination with a tranquilizer. Therefore, it has become well recognized that an optimum agent for treating endogenous depression should possess not only strong anti-depressant properties selective to subjects suffering from endogenous depression as contrasted to normal subjects, but should also have the seemingly antithetical property of having moderate tranquilizing or sedative properties. Accordingly, we have now discovered compounds having the desired combination of anti-depressant and tranquilizing or sedative properties and which can be properly classified as true tranquilizing anti-depressants. In addition, we have discovered compounds having potent anti-depressant activities with insignificant or no tranquilizing activities, which can be classified as pure anti-depressants. Both classes of compounds further exhibit potent antihistamine properties and thus can also be used as antihistamines, preferably in reduced dosages.